Stepharine, an natural alkaloid, directly interactes with TLR4 and binds to the TLR4/MD2 complex (TLR4 inhibitor). Stepharine possesses anti-aging, anti-viral and anti-hypertensive effects.In Vitro: Stepharine (10, 30 μM) substantially inhibits nitric oxide (NO) release as well as the mRNA and protein expression of pro-inflammatory mediators [inducible nitric oxide synthase, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β] in LPS-activated BV-2 cells.
Stepharine (10, 30 μM) inhibits LPS-induced increase of TLR4 expression, IκBα phosphorylation, and NF-κB p65 nuclear translocation.
Stepharine exhibits neuroprotective effects on SH-SY5Y cells cultured with LPS-treated conditioned medium. Stepharine has also shown to inhibit cholinesterase in vitro.
In Vivo: Stepharine (500 μg/kg) inhibited NeuN+ cells loss and Iba-1+ cells increase in the MCAO ischemic cortex.